Metabolic conversion of zearalenone to alpha-zearalenol by goat tissues

Zearalenone (ZEA), an estrogenic mycotoxin produced by several Fusarium species, is converted into a more active metabolite, alpha-zearalenol (alpha-ZOL), and a less active metabolite, beta-zearalenol (beta-ZOL), by liver subcellular fractions, but evidence of this reaction in other tissues is limited. In order to clarify the role of various tissues in ZEA metabolism in ruminant, we investigated the in vitro metabolic conversion of ZEA by various tissues of adult male and female goats. The results indicate that in the liver, alpha-ZOL was a major metabolite in cytosolic fractions, whereas beta-ZOL was a predominant metabolite in microsome fractions. Such a feature of ZEA metabolism was confirmed by the K(m) and V(max) values from an enzyme kinetics experiment. Post-mitochondrial fractions of the liver converted ZEA predominantly to alpha-ZOL, indicating that the goat liver may function as an activation organ rather than as an inactivation organ, for ZEA metabolism in goats. In most other tissues including rumen tissue, the activity converting ZEA to alpha-ZOL was higher than that to beta-ZOL. The amount of alpha-ZOL formed by gastrointestinal tissues was 1/8-1/3 of that by the liver tissue in terms of the amount per mg protein, but the contribution of all gastrointestinal tissues to production of alpha-ZOL was estimated to be comparable to that of the liver because of the large mass of gastrointestinal tissues in ruminants. Overall the results show the importance of not only the liver tissue, but also other tissues, especially gastrointestinal ones, in the formation of a potent estrogenic metabolite, alpha-ZOL.